The 1,2-dihydro-5H-chromeno[3,4-.function.]quinolines of structure 3 are modulators of steroid receptor function. In particular, progesterone receptor (PR) and glucocorticoid receptor (GR) agonist and antagonist activity and androgen receptor (AR) antagonist activity have been noted for compounds in this class. {See: "Preparation of Quinolines and Fused Quinolines as Steroid Receptor Modulators", T. K. Jones, M. E. Goldman, C. L. F. Pooley, D. T. Winn, J. P. Edwards, S. J. West, C. M. Tegley, L. Zhi, L. G. Hamann, R. L. Davis, L. J. Farmer, PCT Int. Appl. Pub. No. WO 96/19458; "Steroid Receptor Modulator Compounds and Methods", T. K. Jones, L. Zhi, J. P. Edwards, C. M. Tegley, S. J. West, U.S. Pat. No. 5,696,127; "5-Aryl-1,2-dihydro-5H-chromeno[3,4-.function.]quinolines as Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists: The Effect of D-Ring Substituents", J. P. Edwards, S. J. West, K. B. Marschke, D. E. Mais, M. M. Gottardis, T. K. Jones, J. Med. Chem. 41 (1998) 303-310.} Chromenoquinolines of structure 3 are prepared by a multi-step route culminating in the addition of an organometallic reagent to a lactone of structure 1 followed by reduction of the hemiketal intermediate 2 (R groups are defined under Detailed Description of the Invention): ##STR1##
Alternatively, certain chromenoquinolines of structure 3 can be prepared in three steps from lactones 1 via acetals 5 by a Lewis-acid mediated nucleophilic substitution reaction using electron-rich olefins or electron-rich aromatic compounds as nucleophiles: ##STR2##
However, these two routes have drawbacks. In the first, the acidic medium required for reduction of hemiketals 2 (R.sup.10 =methyl or ethyl) often promotes the formation of undesired by-products of structure 7: ##STR3##
Additionally, only organolithium reagents add to lactone 1 with generality; for example, many alkyl magnesium halides afford complex mixtures when added to 1. And although certain aryilithium reagents add to the lactone functionality, the resulting hemiketal intermediate 2 cannot be reduced. The versatility of the second route is limited because the third step requires certain electron-rich nucleophiles.